Abstract
This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
Highlights
The ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium is a collaboration of more than 1400 scientists from 43 countries studying the human brain
As we detail in this review, the ENIGMA Consortium has made multiple, seminal contributions to neuroscience and psychiatry, including (a) characterization of robust neuroimaging profiles for various brain disorders, (b) standardization of metrics used to assess clinical symptoms of patients across multiple research sites, and (c) use of dimensional approaches that go beyond the case–control comparisons of individuals with categorical diagnoses, and further enable the investigation of specific genetic, and environmental features or neurobiological markers associated with disorder risk and treatment
Striatal, and hippocampal volumes in the attention-deficit/hyperactivity disorder (ADHD) population, especially in children; lower cortical surface area values found in children with ADHD, but not in adolescents or adults; lower surface area associated with ADHD symptoms in the general population in childhood; genetic association studies suggest that genes involved in neurite outgrowth play a role in findings of reduced volume in ADHD; gene-expression studies imply that structural brain alterations in ADHD can be explained in part by the differential vulnerability of these regions to mechanisms mediating apoptosis, oxidative stress, and autophagy
Summary
ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attentiondeficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors
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